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Daily acyclovir delays HIV-1 disease progression among HIV-1/HSV-2 dually-infected persons: a randomized trial
Presented by Jairam R Lingappa (United States).
J.R. Lingappa1, J.M. Baeten1, A. Wald1,2, J. Hughes1, K.K. Thomas1, A. Mujugira1, N. Mugo1,3, E.A. Bukusi1,3,4, C.R. Cohen5, E. Katabira6, A. Ronald7, J. Kiarie3, C. Farquhar1, G. John-Stewart1, J. Makhema8, M. Essex9, E. Were10, K. Fife11, G. deBruyn12, G. Gray12, J. McIntyre12, R. Manongi13, S. Kapiga14, D. Coetzee15, S. Allen16,17,18, M. Inambao19, K. Kayitenkore18, E. Karita18, W. Kanweka20, S. Delany-Moretlwe12, H. Rees12, B. Vwalika21, A. Magaret1,2, R. Wang1, L. Kidoguchi1, L. Barnes1, R. Ridzon22, L. Corey1,2, C. Celum1, Partners in Prevention HSV/HI
1University of Washington, Seattle, United States, 2Fred Hutchinson Cancer Research Center, Seattle, United States, 3University of Nairobi and Kenyatta National Hospital, Nairobi, Kenya, 4Kenya Medical Research Institute, Nairobi, Kenya, 5University of California, San Francisco, United States, 6Makerere University, Kampala, Uganda, 7University of Manitoba, Winnipeg, Canada, 8Botswana-Harvard Partnership, Gaborone, Botswana, 9Harvard University, Cambridge, United States, 10Moi University, Eldoret, Kenya, 11Indiana University, Indianapolis, United States, 12University of Witwatersrand, Johannesburg, South Africa, 13Kilimanjaro Christian Medical Centre, Moshi, Tanzania, United Republic of, 14London School of Hygiene & Tropical Medicine, London, United Kingdom, 15University of Cape Town, Cape Town, South Africa, 16Emory University, Atlanta, United States, 17Rwanda Zambia HIV Research Group, Ndola, Kitwe, and Lusaka, Zambia, 18Rwanda Zambia HIV Research Group, Kigali, Rwanda, 19Rwanda Zambia HIV Research Group, Ndola, Zambia, 20Rwanda Zambia HIV Research Group, Kitwe, Zambia, 21Rwanda Zambia HIV Research Group, Lusaka, Zambia, 22Bill and Melinda Gates Foundation, Seatlte, United States
Background: Interventions that slow the rate of HIV-1 disease progression and delay initiation of antiretroviral therapy (ART) are needed. Daily HSV-2 suppressive therapy reduced plasma HIV-1 levels in short-term studies among persons dually-infected with HIV-1 and HSV-2, but whether HSV-2 suppression can slow HIV-1 disease progression is unknown.
Methods: We conducted a randomized, placebo-controlled trial of HSV-2 suppressive therapy (acyclovir 400 mg orally bid) among 3381 African women (n=2284) and men (n=1097), dually-infected with HSV-2 and HIV-1, who had CD4 counts ≥250 cells/mm3, and were not taking ART. Participants were followed for ≤ 24 months. The primary composite outcome measure was first occurrence of CD4 count < 200 cells/mm3, ART initiation, or death from non-trauma causes.
Results: Acyclovir reduced the risk of HIV-1 disease progression: 284 participants in the acyclovir arm versus 325 in the placebo arm reached the composite primary endpoint (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71-0.90, p=0.03). Similar magnitude reductions were found for each component of the composite endpoint analyzed separately. Among participants with CD4 counts ≥350 cells/mm3 at enrollment, acyclovir delayed the time to CD4 < 350 cells/mm3 (HR 0.81, 95% CI 0.71-0.93, p=0.002). Number needed to treat calculations demonstrated that 43 persons would need to receive acyclovir for a year to prevent one composite endpoint event, and 20 would need to be treated to prevent one from progressing to a CD4 count < 350 cells/mm3.
Conclusion: Among African women and men dually-infected with HSV-2 and HIV-1 and CD4>250 at enrollment, daily acyclovir HSV-2 suppression reduced the rate of a composite of CD4 decline, need for ART, and mortality. Further evaluation is needed to determine if this 17% reduction in risk of HIV-1 disease progression is sufficient to warrant implementation of HSV-2 suppression as a public health intervention for HIV-1 infected adults not yet requiring ART.
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